Recently ion channels have been shown to interact with cytoskeleton proteins, like PSD families, including PSD93, 95, 97. These PSD proteins all have PDZ domains, which are responsible for interacting with the so-called XV motif at the very C-terminal of the ion channels like K+ channel and glutamate receptors (e.g., NR2A-D). Another PDZ protein, GRIP, interacts with another glutamate receptor, GluR2, which has a different C terminal motif: ISEKI. What determines this specificity? We are now analyzing the crystal structure of the PSD95 PDZ-XV complex. We are also interested in obtaining the crystal structure of GRIP-ISEKI complex. Thus we will be able to pinpoint the determinants responsible for this specific interaction.